PMID- 32930325
OWN - NLM
STAT- MEDLINE
DCOM- 20201216
LR  - 20230413
IS  - 1938-3207 (Electronic)
IS  - 0002-9165 (Print)
IS  - 0002-9165 (Linking)
VI  - 112
IP  - 5
DP  - 2020 Nov 11
TI  - Carbohydrate and fat intake associated with risk of metabolic diseases through 
      epigenetics of CPT1A.
PG  - 1200-1211
LID - 10.1093/ajcn/nqaa233 [doi]
AB  - BACKGROUND: Epigenome-wide association studies identified the cg00574958 DNA 
      methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be 
      associated with reduced risk of metabolic diseases (hypertriglyceridemia, 
      obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism 
      underlying these associations is unknown. OBJECTIVES: We aimed to elucidate 
      whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk 
      of metabolic diseases. METHODS: We examined associations between carbohydrate 
      (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT 
      ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations 
      (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart 
      Study, n = 2331; and REgistre GIroni del COR study, n = 645) while adjusting for 
      confounding factors. To understand possible causal effects of dietary intake on 
      the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription 
      analysis, and mediation analysis with CHO and FAT intakes as exposures and 
      cg00574958 methylation as the mediator. RESULTS: We confirmed strong associations 
      of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) 
      and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT 
      ratio were positively associated with cg00574958 methylation, whereas FAT intake 
      was negatively correlated with cg00574958 methylation. Meta-analysis further 
      confirmed this strong correlation, with beta = 58.4 +/- 7.27, P = 8.98 x 10-16 for CHO 
      intake; beta = -36.4 +/- 5.95, P = 9.96 x 10-10 for FAT intake; and beta = 3.30 +/- 0.49, 
      P = 1.48 x 10-11 for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was 
      negatively associated with CHO intake, and positively associated with FAT intake, 
      and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO 
      intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, 
      whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of 
      metabolic diseases. CONCLUSIONS: Our results suggest that the proportion of total 
      energy supplied by CHO and FAT can have a causal effect on the risk of metabolic 
      diseases via the epigenetic status of CPT1A.Study registration at 
      https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet 
      Network (GOLDN)-NCT01023750; and the Framingham Heart Study (FHS)-NCT00005121.
CI  - Published by Oxford University Press on behalf of the American Society for 
      Nutrition 2020.
FAU - Lai, Chao-Qiang
AU  - Lai CQ
AD  - USDA Agricultural Research Service, Nutrition and Genomics Laboratory, JM-USDA 
      Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
FAU - Parnell, Laurence D
AU  - Parnell LD
AD  - USDA Agricultural Research Service, Nutrition and Genomics Laboratory, JM-USDA 
      Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
FAU - Smith, Caren E
AU  - Smith CE
AD  - Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on 
      Aging at Tufts University, Boston, MA, USA.
FAU - Guo, Tao
AU  - Guo T
AD  - Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on 
      Aging at Tufts University, Boston, MA, USA.
FAU - Sayols-Baixeras, Sergi
AU  - Sayols-Baixeras S
AD  - Cardiovascular Epidemiology and Genetics Research Group, IMIM (Hospital del Mar 
      Medical Research Institute), Barcelona, Catalonia, Spain.
AD  - CIBER Cardiovascular Diseases (CIBERCV), Barcelona, Catalonia, Spain.
AD  - Molecular Epidemiology, Department of Medical Sciences, Uppsala Universitet, 
      Uppsala, Sweden.
FAU - Aslibekyan, Stella
AU  - Aslibekyan S
AD  - Department of Epidemiology, School of Public Health, University of Alabama, 
      Birmingham, AL, USA.
FAU - Tiwari, Hemant K
AU  - Tiwari HK
AD  - Department of Epidemiology, School of Public Health, University of Alabama, 
      Birmingham, AL, USA.
FAU - Irvin, Marguerite R
AU  - Irvin MR
AD  - Department of Epidemiology, School of Public Health, University of Alabama, 
      Birmingham, AL, USA.
FAU - Bender, Carl
AU  - Bender C
AD  - Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on 
      Aging at Tufts University, Boston, MA, USA.
FAU - Fei, David
AU  - Fei D
AD  - Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on 
      Aging at Tufts University, Boston, MA, USA.
FAU - Hidalgo, Bertha
AU  - Hidalgo B
AD  - Department of Epidemiology, School of Public Health, University of Alabama, 
      Birmingham, AL, USA.
FAU - Hopkins, Paul N
AU  - Hopkins PN
AD  - Department of Cardiovascular Genetics, University of Utah, Salt Lake City, UT, 
      USA.
FAU - Absher, Devin M
AU  - Absher DM
AD  - Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA.
FAU - Province, Michael A
AU  - Province MA
AD  - Department of Genetics, Washington University School of Medicine, St Louis, MO, 
      USA.
FAU - Elosua, Roberto
AU  - Elosua R
AD  - Cardiovascular Epidemiology and Genetics Research Group, IMIM (Hospital del Mar 
      Medical Research Institute), Barcelona, Catalonia, Spain.
AD  - CIBER Cardiovascular Diseases (CIBERCV), Barcelona, Catalonia, Spain.
FAU - Arnett, Donna K
AU  - Arnett DK
AD  - College of Public Health, University of Kentucky, Lexington, KY, USA.
FAU - Ordovas, Jose M
AU  - Ordovas JM
AD  - Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on 
      Aging at Tufts University, Boston, MA, USA.
AD  - IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
AD  - Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT00005121
SI  - ClinicalTrials.gov/NCT01023750
GR  - P30 DK056341/DK/NIDDK NIH HHS/United States
GR  - P30 DK079626/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Am J Clin Nutr
JT  - The American journal of clinical nutrition
JID - 0376027
RN  - 0 (Dietary Carbohydrates)
RN  - 0 (Dietary Fats)
RN  - EC 2.3.1.21 (CPT1A protein, human)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carnitine O-Palmitoyltransferase/genetics/*metabolism
MH  - Dietary Carbohydrates/*adverse effects
MH  - Dietary Fats/*adverse effects
MH  - *Epigenesis, Genetic
MH  - Epigenome
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Genetic Variation
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Male
MH  - Middle Aged
PMC - PMC7657341
OTO - NOTNLM
OT  - CPT1A
OT  - carbohydrate and fat intake
OT  - diabetes
OT  - dyslipidemia
OT  - epigenetics
OT  - hypertension
OT  - metabolic syndrome
OT  - obesity
EDAT- 2020/09/16 06:00
MHDA- 2020/12/17 06:00
PMCR- 2020/09/15
CRDT- 2020/09/15 08:53
PHST- 2020/03/16 00:00 [received]
PHST- 2020/07/23 00:00 [accepted]
PHST- 2020/09/16 06:00 [pubmed]
PHST- 2020/12/17 06:00 [medline]
PHST- 2020/09/15 08:53 [entrez]
PHST- 2020/09/15 00:00 [pmc-release]
AID - S0002-9165(22)00891-7 [pii]
AID - nqaa233 [pii]
AID - 10.1093/ajcn/nqaa233 [doi]
PST - ppublish
SO  - Am J Clin Nutr. 2020 Nov 11;112(5):1200-1211. doi: 10.1093/ajcn/nqaa233.